Study Reveals Breakthrough Discovery: How Cancer Outsmarts the Immune System
Research into immunotherapy against cancer typically focuses on better recognition of cancer cells by the body's own immune system.
Researchers at Amsterdam UMC and Moffitt Cancer Center have investigated how cancer affects the energy management of a patient’s T cells and showed for the first time that contact with chronic lymphocytic leukaemia (CLL) cells leads to a serious energy crisis in these cells. These findings are published in Cellular & Molecular Immunology.
CLL is the most common type of leukaemia in the Western world and mainly affects the elderly. Despite new therapies, the disease remains incurable, and treatments are becoming increasingly expensive.
"Our research revealed two things to us: firstly, that healthy T cells greatly increase their absorption of cholesterol and fats after they have identified their targets. Without this fuel, they are unable to proliferate. Secondly, and crucially, that this doesn't happen when T cells come into close contact with leukemia cells,” says Arnon Kater, professor of Translational Haematology at Amsterdam UMC.
This discovery brings us one step closer to making CAR T-cell treatment more successful for a greater number of patients. More importantly, it opens the door for exploring similar strategies in other cancers where immune cells struggle to sustain their attack. By addressing the energy crisis in T cells, we hope to enhance immunotherapy across a wider range of cancers,” he adds.
Hence, the researchers concluded that a faulty lipid regulation at the transcriptional level, results in altered lipid composition and utilization in CLL T cells, contributing to T-cell dysfunction at multiple levels, the most important being impaired lipid raft formation and proliferation due to lack of cholesterol and phospholipids, and compromised bioenergetics by lower FAO. Thus, altered lipid metabolism constitutes an integral explanation for altered T-cell function in CLL.
Ref: Jacobs, C.F., Peters, F.S., Camerini, E. et al. Cholesterol homeostasis and lipid raft dynamics at the basis of tumor-induced immune dysfunction in chronic lymphocytic leukemia. Cell Mol Immunol (2025). https://doi.org/10.1038/s41423-025-01262-1
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